Assay devices with integrated sample dilution and dilution verification and methods of using same

• US 9,841,396 B2
• Filed: 05/01/2015
• Issued: 12/12/2017
• Est. Priority Date: 12/03/2010
• Status: Active Grant

• Current Assignee: Abbott Point Of Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Point Of Care Incorporated (Abbott Laboratories Incorporated)
• Inventors: Miller, Cary James, Davis, Graham, Zelin, Michael
• Primary Examiner(s): BROWN, MELANIE YU
• Application Number:
  US14/702,594
• Publication Number:
  US 20150233862A1
• Time in Patent Office: 956 Days
• CPC Class Codes: B01F 31/65 the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/045 whereby the whole cover is slidable
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0672 Integrated piercing tool
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/126 Paper
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0672 Swellable plugs
• CPC Class Codes: B01L 3/502 with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: G01N 21/25 Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
• CPC Class Codes: G01N 21/78 producing a change of colour
• CPC Class Codes: G01N 27/02 by investigating impedance
• CPC Class Codes: G01N 27/26 by investigating electrochemical variables; by using electrolysis or electrophoresis
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• CPC Class Codes: G01N 27/3274 : Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771
• CPC Class Codes: G01N 27/413 : Concentration cells using liquid electrolytes measuring currents or voltages in voltaic cells
• CPC Class Codes: G01N 27/49 : Systems involving the determination of the current at a single specific value, or small range of values, of applied voltage for producing selective measurement of one or more particular ionic species
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54373 : involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/76 : Human chorionic gonadotropin including luteinising hormone, follicle stimulating hormone, thyroid stimulating hormone or their receptors

Abstract

The invention is to devices and method for rapid determination of analytes in liquid samples by various assays including immunoassays incorporating a sample dilution feature for forming a diluted sample for analysis. The devices and methods also include a dilution verification feature for verifying the degree of dilution of the diluted sample. The devices preferably are capable of being used in the point-of-care diagnostic field is provided.

Claims

1. A method of performing an assay for an analyte in a sample, said method comprising the steps of:

introducing a sample into a sample chamber of a cartridge, wherein said chamber is located between a sample entry port and a sample isolation unit and includes a diluent introduction port for receiving diluent, and wherein the volume between the diluent introduction port and the sample isolation unit defines a metered volume of said sample for dilution;

transporting a volume of diluent from a diluent conduit to the metered volume of sample, wherein said volume of diluent is combined with said metered volume of sample to form a diluted sample;

transporting said diluted sample to a sensor;

performing an analyte assay at said sensor; and

determining a dilution ratio of the diluted sample.

2. The method of claim 1, further comprising adding a dilution determinant marker to said sample, wherein said dilution ratio is characterized using the dilution determinant marker.

3. The method of claim 2, wherein said dilution determinant marker is selected from the group consisting of an electrochemical species, ferricyanide, ruthenium hexamine, a ferrocene, ferrocene monocarboxylic acid, an optical dye, fluorescein, an acridinium salt, and methylene blue.

4. The method of claim 2, wherein the dilution determinant marker concentration is measured using an electrochemical analysis system for amperometric measurements.

5. The method of claim 2, wherein the dilution determinant marker concentration is measured using a potentiometric sensor.

6. The method of claim 2, wherein the dilution determinant marker concentration is measured using a spectrophotometer.

7. The method of claim 1, wherein the at least one analyte for sensing is CRP.

8. The method of claim 1, wherein the volume of diluent comprises a metered volume of diluent.

9. The method of claim 8, wherein the cartridge includes a pump conduit beginning at a pump and ending at an air introduction port on the diluent conduit, and wherein a region in the diluent conduit between the air introduction port and the diluent introduction port defines the metered volume of diluent.

10. The method of claim 1, wherein the sample is selected from the group consisting of blood, plasma, serum, urine, interstitial fluid and cerebrospinal fluid.

11. The method of claim 1, wherein said sample isolation unit comprises a capillary stop.

12. The method of claim 1, wherein said sample isolation unit is selected from the group consisting of a porous hydrophilic material, a cellulose material, nitrocellulose, cotton fiber, paper, and glass-filled paper.

13. The method of claim 1, wherein the diluted sample is at a dilution ratio of from 1:

1 to 50;

1 parts by volume diluent;

sample.

14. The method of claim 1, wherein the volume of the diluent is a metered volume of the diluent defined by a volume within a portion of the diluent conduit.

15. The method of claim 14, wherein the metered volume of the diluent and the metered volume of the sample are used to provide the dilution ratio.

16. The method of claim 15, further comprising adding a predetermined known amount of a dilution determinant marker to said sample, wherein said dilution ratio is determined using the dilution determinant marker.

17. The method of claim 16, wherein the determining comprises determining the dilution ratio of the diluted sample from a measured concentration of the dilution determinant marker in the diluted sample and the predetermined known amount of the dilution determinant marker.

18. The method of claim 17, further comprising calculating a concentration of an analyte in the sample based on the performing the analyte assay on the diluted sample and the determined dilution ratio.

19. The method of claim 18, wherein the predetermined known amount is an embedded value on the cartridge.

20. The method of claim 16, further comprising introducing the diluted sample to a reagent comprising a conjugate molecule, wherein the dilution determinant marker is a different entity from that of the conjugate molecule.